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1. 发明申请

US20220054433A1 AGENTS FOR REVERSING TOXIC PROTEINOPATHIES 有权
公开(公告)号：US20220054433A1
公开(公告)日：2022-02-24
申请号：US17494824
申请日：2021-10-05
申请人： THE BROAD INSTITUTE, INC. , THE BRIGHAM & WOMEN'S HOSPITAL, INC. , DANA-FARBER CANCER INSTITUTE, INC. , Instituto Carlos Slim de la Salud, A.C.
发明人： Anna Greka , Moran Dvela-Levitt , Maria Alimova , Eric Lander , Todd R. Golub , Florence Wagner , Brian Chamberlain , Valeria Padovano , Joseph Growney
IPC分类号： A61K31/13 , A61P27/02 , A61P13/12 , C12Q1/6883
摘要： The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of proteinopathies, particularly MUC1-associated kidney disease (ADTKD-MUC1 or MKD), Retinitis Pigmentosa (e.g., due to rhodopsin mutations), autosomal dominant tubulo-interstitial kidney disease due to UMOD mutation(s) (ADTKD-UMOD), and other forms of toxic proteinopathies resulting from mutant protein accumulation in the ER or other secretory pathway compartments and/or vesicles, among others. The disclosure also identifies and provides TMED9-binding agents as capable of treating or preventing proteinopathies of the secretory pathway, and further provides methods for identifying additional TMED9-binding agents.

2. 发明授权

US10345297B2 Genetically encoded biosensors 有权
公开(公告)号：US10345297B2
公开(公告)日：2019-07-09
申请号：US16112481
申请日：2018-08-24
申请人： Howard Hughes Medical Institute , The Brigham & Women's Hospital, Inc.
发明人： Jonathan S. Marvin , Loren Looger , Richard T. Lee , Eric Schreiter
IPC分类号： G01N33/557 , C07K14/245 , C07K14/435 , G01N33/68 , C07K14/195 , G01N33/58
摘要： The present disclosure provides, inter alia, genetically encoded recombinant peptide biosensors comprising analyte-binding framework portions and signaling portions, wherein the signaling portions are present within the framework portions at sites or amino acid positions that undergo a conformational change upon interaction of the framework portion with an analyte.

3. 发明授权

US12048676B2 Agents for reversing toxic proteinopathies 有权
公开(公告)号：US12048676B2
公开(公告)日：2024-07-30
申请号：US17494830
申请日：2021-10-06
申请人： THE BROAD INSTITUTE, INC. , THE BRIGHAM & WOMEN'S HOSPITAL, INC. , DANA-FARBER CANCER INSTITUTE, INC. , Instituto Carlos Slim de la Salud, A.C.
发明人： Anna Greka , Moran Dvela-Levitt , Maria Alimova , Eric Lander , Todd R Golub , Florence Wagner , Brian Chamberlain , Valeria Padovano , Joseph Growney
IPC分类号： A61K31/13 , A61P13/12 , A61P27/02 , C12Q1/6883
CPC分类号： A61K31/13 , A61P13/12 , A61P27/02 , C12Q1/6883
摘要： The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of proteinopathies, particularly MUC1-associated kidney disease (ADTKD-MUC1 or MKD), Retinitis Pigmentosa (e.g., due to rhodopsin mutations), autosomal dominant tubulo-interstitial kidney disease due to UMOD mutation(s) (ADTKD-UMOD), and other forms of toxic proteinopathies resulting from mutant protein accumulation in the ER or other secretory pathway compartments and/or vesicles, among others. The disclosure also identifies and provides TMED9-binding agents as capable of treating or preventing proteinopathies of the secretory pathway, and further provides methods for identifying additional TMED9-binding agents.

4. 发明申请

US20220404336A1 COMPOSITIONS, METHODS AND USES FOR FREE FATTY ACID SCREENING OF CELLS AT SCALE 有权
公开(公告)号：US20220404336A1
公开(公告)日：2022-12-22
申请号：US17641683
申请日：2020-09-09
申请人： THE BROAD INSTITUTE, INC. , THE BRIGHAM & WOMEN'S HOSPITAL, INC. , PRESIDENT AND FELLOWS OF HARVARD COLLEGE
发明人： Anna Greka , Nicolas Wieder , Juliana Coraor
IPC分类号： G01N33/50 , C07K14/765 , C07K1/107 , C12Q1/6883
摘要： The present disclosure relates to compositions and methods for the preparation and use of free fatty acids as crystals and in solution, optionally in array format, for assay of lipotoxicity and related effects (in certain cases, indicators of diseases or disorders, such as type II diabetes) in contacted cells. Identification and therapeutic targeting of high-value gene targets discovered via joint assessment of lipotoxicity/transcriptome data and genetic association study data are also provided.

5. 发明授权

US11160808B2 Compounds that enhance Atoh1 expression 有权
公开(公告)号：US11160808B2
公开(公告)日：2021-11-02
申请号：US16518788
申请日：2019-07-22
申请人： Massachusetts Eye & Ear Infirmary , The Brigham & Women's Hospital, Inc.
发明人： Albert Edge , Sang-Jun Jeon , Kathleen Seyb , Marcie Glicksman , Lixin Qiao , Gregory D. Cuny
IPC分类号： A61K31/5377 , A61K31/343 , A61K31/381 , A61K31/415 , A61K31/423 , A61K31/4245 , A61K31/426 , A61K31/428 , A61K31/341 , A61K31/4184 , A61K9/00 , A61K31/353 , A61K31/4436 , A61K31/496 , A61K31/498 , A61K31/517 , A61K31/519 , A61K35/28 , A61K35/545 , A61K31/352 , A61K31/404 , A61K31/4155 , A61K31/4192 , A61K31/4365 , A61K31/437 , A61K31/44 , A61K31/4439
摘要： This invention generally provides compounds, pharmaceutical compositions, and methods for their use, which include methods that result in increased expression in an Atoh1 gene (e.g., Hath1) in a biological cell. More specifically, the invention relates to the treatment of diseases and/or disorders that would benefit from increased Atoh1 expression, e.g., a hearing impairment or imbalance disorder associated with a loss of auditory hair cells, or a disorder associated with abnormal cellular proliferation.

6. 发明申请

US20180372738A1 GENETICALLY ENCODED BIOSENSORS 审中-公开
公开(公告)号：US20180372738A1
公开(公告)日：2018-12-27
申请号：US16112481
申请日：2018-08-24
申请人： Howard Hughes Medical Institute , The Brigham & Women's Hospital, Inc.
发明人： Jonathan S. Marvin , Loren Looger , Richard T. Lee , Eric Schreiter
IPC分类号： G01N33/557 , C07K14/245 , C07K14/435 , G01N33/68 , C07K14/195 , G01N33/58
CPC分类号： G01N33/557 , C07K14/195 , C07K14/245 , C07K14/43595 , C07K2319/20 , C07K2319/24 , C07K2319/60 , G01N33/582 , G01N33/68 , G01N33/6812 , G01N2400/00 , G01N2458/00
摘要： The present disclosure provides, inter alia, genetically encoded recombinant peptide biosensors comprising analyte-binding framework portions and signaling portions, wherein the signaling portions are present within the framework portions at sites or amino acid positions that undergo a conformational change upon interaction of the framework portion with an analyte.

7. 发明授权

US09939437B2 Genetically encoded biosensors 有权
公开(公告)号：US09939437B2
公开(公告)日：2018-04-10
申请号：US15664326
申请日：2017-07-31
申请人： Howard Hughes Medical Institute , The Brigham & Women's Hospital, Inc.
发明人： Jonathan S. Marvin , Loren Looger , Richard T. Lee , Eric Schreiter
IPC分类号： G01N33/557 , G01N33/68 , G01N33/58 , C07K14/195 , C07K14/245 , C07K14/435
CPC分类号： G01N33/557 , C07K14/195 , C07K14/245 , C07K14/43595 , C07K2319/20 , C07K2319/24 , C07K2319/60 , G01N33/582 , G01N33/68 , G01N33/6812 , G01N2400/00 , G01N2458/00
摘要： The present disclosure provides, inter alia, genetically encoded recombinant peptide biosensors comprising analyte-binding framework portions and signaling portions, wherein the signaling portions are present within the framework portions at sites or amino acid positions that undergo a conformational change upon interaction of the framework portion with an analyte.

8. 发明申请

US20140193906A1 SCREENING METHODS FOR SPINAL MUSCULAR ATROPHY 有权
标题翻译：脊柱肌肉切除术的筛选方法
公开(公告)号：US20140193906A1
公开(公告)日：2014-07-10
申请号：US13941099
申请日：2013-07-12
申请人： Indiana University Research and Technology Corporation , The University of Massachusetts , The Brigham Women's Hospital, Inc.
发明人： Elliot Androphy , Gregory D. Cuny , Jonathan Cherry , Marcie A. Glicksman
IPC分类号： C07K14/47
CPC分类号： C07D493/04 , C07C311/37 , C07C2601/08 , C07C2603/20 , C07D213/75 , C07D215/227 , C07D215/44 , C07D221/10 , C07D231/14 , C07D233/88 , C07D239/47 , C07D239/82 , C07D261/06 , C07D261/14 , C07D261/18 , C07D263/48 , C07D267/14 , C07D277/46 , C07D285/135 , C07D401/04 , C07D405/04 , C07D405/12 , C07D413/12 , C07D417/04 , C07D417/12 , C07D471/04 , C07D487/04 , C07K14/47
摘要： Disclosed herein are compositions and methods for treatment of spinal muscular atrophy (SMA). In certain embodiments, compounds are provided that increase full-length survival of motor neuron (SMN) protein production by an SMN2 gene.
摘要翻译：本文公开了用于治疗脊髓性肌萎缩（SMA）的组合物和方法。在某些实施方案中，提供了通过SMN2基因增加运动神经元（SMN）蛋白质产生的全长存活的化合物。

9. 发明申请

US20210177827A1 PAPD5 INHIBITORS AND METHODS OF USE THEREOF 有权
公开(公告)号：US20210177827A1
公开(公告)日：2021-06-17
申请号：US16758804
申请日：2018-10-25
申请人： Children`s Medical Center Corporation , The Brigham & Women's Hospital, Inc.
发明人： Suneet Agarwal , Neha Nagpal , Yick Fong
IPC分类号： A61K31/4706 , A61K31/4365 , A61K31/4245 , A61K31/549 , A61K31/4025 , A61K31/519 , A61K31/506 , A61K31/4709 , A61K31/473 , A61K31/47 , A61K31/517 , A61K31/5377 , A61K31/52 , A61K31/5025 , A61K31/502 , A61K31/472 , A61K31/4375 , A61K31/499 , A61K31/551 , A61K31/498 , A61K31/4985 , A61K31/4741 , A61K31/496 , A61K31/4178 , A61K31/404 , A61K31/422 , A61K31/433 , A61K31/4188 , A61K31/353 , A61K31/437 , A61K31/53 , A61K31/4162 , A61K31/429 , A61K31/55 , A61K31/381 , A61K31/428 , A61K31/538 , A61K31/5415 , A61K31/341 , C12Q1/66
摘要： The disclosure relates to compounds that are, e.g., PAP Associated Domain Containing 5 (PAPD5) inhibitors and methods of use thereof.

10. 发明申请

US20160115112A1 NOVEL N-3 IMMUNORESOLVENTS: STRUCTURES AND ACTIONS 有权
标题翻译：新型N-3免疫球蛋白：结构和作用
公开(公告)号：US20160115112A1
公开(公告)日：2016-04-28
申请号：US14894921
申请日：2014-05-14
申请人： THE BRIGHAM & WOMEN'S HOSPITAL INC.
发明人： Charles N. SERHAN , Jesmond DALLI
IPC分类号： C07C57/03 , C07D303/38
CPC分类号： C07C57/03 , C07D303/38
摘要： The invention describes novel mono-hydroxy, di-hydroxy and tri-hydroxy docosapentaenoic acid (DPA) analogues, their preparation, isolation, identification, purification and uses thereof. Resolution of inflammation is now held to be an active process where autacoids promote homeostasis. Using functional-metabololipidomics and in vivo systems, endogenous n-3 docosapentaenoic (DPA) acid is converted during inflammation-resolution in mice and by human leukocytes to novel n-3 products congenerous to D-series resolvins (Rv), protectins (PD) and maresins (MaR), termed specialized pro-resolving mediators (SPM). The new n-3 DPA structures include 7,8,17-trihydroxy-9,11,13,15E,19Zdocosapentaenoic acid (RvD1n_3 DPA), 7,14-dihydroxy-8,10,12,16Z,19Z-docosapentaenoic acid (MaR1n_3 DPA) and related bioactive products.
摘要翻译：本发明描述了新的单羟基，二羟基和三羟基二十二碳烯酸（DPA）类似物，其制备，分离，鉴定，纯化和用途。炎症的解决方案现在被认为是一种活性过程，其中自发性促进促进体内平衡。使用功能代谢组脂蛋白和体内系统，内源性n-3二十二碳烯酸（DPA）酸在小鼠和人类白细胞的炎症分解过程中转化为与D系列溶解素（Rv），保护素（PD）一致的新型n-3产物，和马林（MaR），称为专门解析调解员（SPM）。新的n-3DPA结构包括7,8,17-三羟基-9,11,13,15E，19Z二十碳五烯酸（RvD1n_3DPA），7,14-二羟基-8,10,12,16Z，19Z-二十二碳五烯酸 MaR1n_3 DPA）及相关生物活性产品。

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